Exocrine pancreas function decreases during the progression of the beta‐cell damaging process in young prediabetic children

Kondrashova, Anita; Nurminen, Noora; Lehtonen, Jussi; Hyöty, Marja; Toppari, Jorma; Ilonen, Jorma; Veijola, Riitta; Knip, Mikael; Hyöty, Heikki

doi:10.1111/pedi.12592

Cited by 23 publications

(21 citation statements)

References 18 publications

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“…[3,4] For example, a recent study found significant decrease in the levels of elastase, a serine protease marker for pancreas exocrine function, in T1D children but not in autoantibody positive cases relative to controls, suggesting impaired exocrine function in T1D pancreas. [5] This is in line with previous findings of pancreatic exocrine deficiency in 25%-74% of T1D patients, [6] and the association of T1D patients with pancreas volume and size reduction. [7,8] In addition, autoantibodies of exocrine carbonic anhydrase and lactoferrin are observed in exocrine pancreas [9] and infiltration of immune cells can also occur in exocrine pancreas, which indicates the existence of inflammation in the exocrine pancreas is similar to what observed in the endocrine pancreas.…”

Section: Introductionsupporting

confidence: 91%

Pancreatic Tissue Proteomics Unveils Key Proteins, Pathways, and Networks Associated with Type 1 Diabetes

Woo

Sudhir

Zhang

2020

Proteomics Clinical Apps

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Purpose: Type 1 diabetes (T1D) is characterized by autoimmune mediated self-destruction of the pancreatic islet beta cells and the resultant insulin deficiency. However, little is known about the underlying molecular pathogenesis at the pancreatic tissue level given the limited availability of clinical specimens. Experimental Design: Quantitative proteomic studies is performed on age-matched T1D and healthy cadaveric pancreatic tissues (n = 18 each) using TMT 10plex-based isobaric labeling and BoxCar-based label-free LC-MS/MS approaches. ELISA is used to validate the differentially expressed proteins (DEPs). Results: Overall, the two quantitative proteomics approaches identified 8824 proteins, of which 261 are DEPs. KEGG pathway and functional network analyses of the DEPs reveal dysregulations to pancreatic exocrine function, complement coagulation cascades, and extracellular matrix receptor interaction pathways in T1D. A selected list of the DEPs associated with pathways, subnetworks, and plasma proteome of T1D are validated using ELISA. Conclusions and Clinical Relevance: Integrating labeling and label-free approaches improve the confidence in quantitative profiling of pancreatic tissue proteome, which furthers the understanding of the dysregulated pathways and functional subnetworks associated with T1D pathogenesis and may aid to develop diagnostic and therapeutic strategies for T1D.

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Section: Introductionsupporting

confidence: 91%

Pancreatic Tissue Proteomics Unveils Key Proteins, Pathways, and Networks Associated with Type 1 Diabetes

Woo

Sudhir

Zhang

2020

Proteomics Clinical Apps

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“…Similar inflammatory cells are found also in exocrine pancreas, and the whole organ is decreased in size with different structural changes . Furthermore, it is found that the exocrine function decreases gradually in individuals already before they get manifest T1D, and exocrine function is decreased in many children with T1D . It has been known for very long time that infections of pancreas can lead to T1D and also diabetes‐related autoimmunity, and it has been asked whether mild virus or bacterial infections causing pancreatitis could be one common cause of T1D.…”

Section: Discussionmentioning

confidence: 99%

No acute pancreatitis but reduced exocrine pancreatic function at diagnosis of type 1 diabetes in children

Ludvigsson

2019

Pediatr Diabetes

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Background Insulitis in type 1 diabetes (T1D) seems to be both mild and rather rare, and immune cells are found also in the exocrine pancreas, which often is small. We wanted to see whether clinical pancreatitis at diagnosis of T1D in children is a commonly missed diagnosis. Methods Clinical symptoms suggesting pancreatitis were investigated in a retrospective case‐control study in 191 newly diagnosed T1D patients (105 boys, 86 girls) with age at onset 0.2 to 18 (mean = 10.05, SD = 4.71, median = 10.36) years, 23/191 (12%) with ketoacidosis at diagnosis. Blood samples were taken on day 4 and stored at −20°C until analyses for P‐amylase and C‐reactive protein (CRP), and compared with 100 age‐matched healthy control children with plasma stored at −80°C, and 46 with plasma stored at −20°C. Results At diagnosis, 23/191 (12%) patients had mild transient abdominal pain, 2/23 with obstipation, and 5/23 also transient mild diarrhea. Five of 23 patients with abdominal pain had pH < 7.30. None had clinical acute pancreatitis. One diabetic patient had P‐amylase 1.3 μkat/L (normal range = 0.15‐1.1 μkat/L), while 62/191 (32.4%) diabetic children had P‐amylase below the normal range. None (0/100) of the −80‐controls and only 1/46 (0.14 μkat/L) of the −20‐controls had the P‐amylase level in the normal range. Five diabetic children, but no controls, had increased CRP, but not related to P‐amylase or to gastrointestinal symptoms. Conclusions Acute pancreatitis seems to be very rare at diagnosis of T1D, but decreased exocrine function quite common, which supports that T1D sometimes is part of a more generalized pancreatic disorder.

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“…Since islets constitute only a small portion of the pancreatic mass, these reductions seem to be largely attributable to a significant exocrine tissue loss. In support of this concept, a decline in exocrine function (evaluated by chymotrypsin and elastase stool measurement) has been observed . Finally, an exocrine pancreatopathy (defined as a moderate‐to‐severe subclinical fibrosis and modest exocrine dysfunction, occurring in the absence of clinical or histopathological evidence of chronic pancreatitis) has been described to be associated with pancreatic size in T1D.…”

Section: Pancreas Anatomical Alterations In T1dmentioning

confidence: 83%

From immunohistological to anatomical alterations of human pancreas in type 1 diabetes: New concepts on the stage

Nigi

Maccora

Dotta

et al. 2019

Diabetes Metabolism Res

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The histological analysis of human pancreatic samples in type 1 diabetes (T1D) has been proven essential to move forward in the evaluation of in situ events characterizing T1D. Increasing availability of pancreatic tissues collected from diabetic multiorgan donors by centralized biorepositories, which have shared tissues among researchers in the field, has allowed a deeper understanding of T1D pathophysiology, using novel immunohistological and high-throughput methods. In this review, we provide a comprehensive update of the main recent advancements in the characterization of cellular and molecular events involving endocrine and exocrine pancreas as well as the immune system in the onset and progression of T1D. Additionally, we underline novel elements, which provide evidence that T1D pathological changes affect not only islet β-cells but also the entire pancreas.

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Exocrine pancreas function decreases during the progression of the beta‐cell damaging process in young prediabetic children

Abstract: The results suggest that the defect in the exocrine function develops after the appearance of islet autoantibodies. Further studies are needed to assess whether reduced elastase levels predict rapid progression of islet autoimmunity to clinical disease.

Cited by 23 publications

References 18 publications

Pancreatic Tissue Proteomics Unveils Key Proteins, Pathways, and Networks Associated with Type 1 Diabetes

Pancreatic Tissue Proteomics Unveils Key Proteins, Pathways, and Networks Associated with Type 1 Diabetes

No acute pancreatitis but reduced exocrine pancreatic function at diagnosis of type 1 diabetes in children

From immunohistological to anatomical alterations of human pancreas in type 1 diabetes: New concepts on the stage

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